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Genetic Minimalism

By Sean Henahan, Access Excellence

Chapel Hill, NC (12/10/99)- The discovery of the minimum numbers of genes required to produce a living organism will make it possible for scientists to create new life forms from scratch, a prospect likely to spur considerable ethical debate.

gene mapResearcher Dr. Clyde A. Hutchison III, professor of microbiology at the University of North Carolina, and colleagues began with Mycoplasma genitalium, the smallest known genome capable of independent replication, with 517 genes. Using a a process of elimination strategy called global transposon mutagenesis, the researchers disrupted the genes one at a time to determine which were essential for survival. This revealed that 255 to 340 of protein-coding genes were essential to life.

"Cells that grow and divide after this procedure can have such disruptive insertions only in nonessential genes. Surprisingly, the minimal set of genes we found included about 100 whose function we don't yet understand. This finding calls into question the prevailing assumption that the basic molecular mechanisms underlying cellular life are understood, at least broadly," said Dr. Hutchison.

Image- Genome Map of M. genitalium (click to enlarge)
Credit: Owen White, TIGR

While the researchers took a giant step towards creating life, they did not produce any new life forms. Defining the minimal set of genes required for an organism to survive in the lab is the first step. There are more elements to basic life. It is also essential to know what other cellular components such as proteins and sugars are needed for metabolism and replication. Another major challenge will be learning how to assemble all of these elements along with DNA.

The ability to create organisms from new and existing genomes would further accelerate the rapid rate of development of genetic engineering and biotechnology. Research in this area could also contribute to the basic understanding of how life originated and evolved on the planet.

"The prospect of constructing minimal and new genomes does not violate any fundamental moral precepts or boundaries, but does raise questions that are essential to consider before the technology advances further. How does work on minimal genomes and the creation of new free-living organisms change how we frame ideas of life and our relationship to it? How can the technology be used for the benefit of all, and what can be done in law and social policy to ensure that outcome?" asked Dr. Mildred K. Cho of the Stanford University Center for Biomedical Ethics in an essay in the journal Science.

"The temptation to demonize this fundamental research may be irresistible," she said. "However, the scientific community and the public can begin to understand what is at stake if efforts are made now to identify the nature of the science involved and to pinpoint key ethical, religious and metaphysical questions."

This new direction in biotechnology could accelerate the pace at which genetically modified organisms are developed.with unknown and unpredictable effects on the environment. Unraveling the genomes of harmful bacteria could lead to new kinds of treatments for infectious disease. However, this knowledge could also be used to create new infectious agents that could be d as biological weapons. Ultimately, it might be possible to create modified forms of more advanced life forms, up to and including humans.

For all of these and many other reasons, it is important that avenues of communication and discussion among scientists, religious leaders, biomedical ethicists and the public remain open regarding the various implications of this new direction in biological research, Cho stressed.

The research appears appears in the Dec.10, 1999 issue of the journal Science.

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